HCID 117974161, compound → HCID 117974138, compound

HRID 1776124Notes

Reaction equation

HRID 1776124 reaction equation
[CH:1]1([CH2:4][O:5][C@H:6]2[C@H:14]([CH3:15])[O:13][C:12](=[O:16])[C@@H:11]([NH:17][C:18](=[O:28])[C:19]3[C:24]([OH:25])=[C:23]([O:26][CH3:27])[CH:22]=[CH:21][N:20]=3)[CH2:10][CH2:9][CH2:8][C@@H:7]2[CH2:29][C:30]2[CH:35]=[CH:34][C:33](F)=[CH:32][CH:31]=2)[CH2:3][CH2:2]1>C1COCC1.[Rh]>[CH:30]1([CH2:29][C@@H:7]2[C@@H:6]([O:5][CH2:4][CH:1]3[CH2:2][CH2:3]3)[C@H:14]([CH3:15])[O:13][C:12](=[O:16])[C@@H:11]([NH:17][C:18](=[O:28])[C:19]3[C:24]([OH:25])=[C:23]([O:26][CH3:27])[CH:22]=[CH:21][N:20]=3)[CH2:10][CH2:9][CH2:8]2)[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

4

Reactant 1

HCID 117974161HCID 117974161, compound

Product 1

HCID 117974138HCID 117974138, compoundYield 27.1%

Reagents, catalysts & solvents 2

HCID 23948RhodiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A high pressure reactor equipped with a stir bar was charged with a solution of N-((3S,7R,8R,9S)-8-(cyclopropylmethoxy)-7-(4-fluorobenzyl)-9-methyl-2-oxooxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (230 mg, 0.459 mmol) in THF (7 mL) and 5% rhodium on carbon (56.8 mg, 0.028 mmol). After the reactor was sealed and purged with H2 (4×), the reaction was charged to ˜600 psi of H2 at room temperature. The reactor was warmed to 70° C. and stirred for 29 h, cooled to room temperature, and the reaction mixture was filtered through a Celite® pad. The filtrate was concentrated and purified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate) to furnish the title product as a white solid (60.8 mg, 27%): 1H NMR (400 MHz, CDCl3) δ 12.11 (d, J=0.6 Hz, 1H), 8.49 (d, J=8.2 Hz, 1H), 7.99 (d, J=5.2 Hz, 1H), 6.87 (d, J=5.2 Hz, 1H), 4.95-4.84 (m, 1H), 4.55 (ddd, J=10.7, 8.2, 7.0 Hz, 1H), 3.94 (s, 3H), 3.49 (dd, J=9.6, 7.0 Hz, 1H), 3.37 (dd, J=9.6, 6.8 Hz, 1H), 3.01 (t, J=8.8 Hz, 1H), 2.39-2.28 (m, 1H), 1.78-1.46 (m, 10H), 1.45 (d, J=7.0 Hz, 3H), 1.41-0.71 (m, 10H), 0.59-0.52 (m, 2H), 0.26-0.18 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 172.21, 168.62, 155.31, 148.69, 140.51, 130.42, 109.44, 84.33, 78.51, 75.66, 56.05, 51.49, 40.09, 38.30, 35.05, 34.59, 33.63, 32.34, 27.44, 26.68, 26.48, 26.15, 18.77, 18.10, 11.14, 3.16, 2.94; ESIMS m/z 489.3 ([M+H]+).

Workup

  1. customA high pressure reactor equipped with a stir bar
  2. customAfter the reactor was sealed
  3. custompurged with H2 (4×)
  4. additionthe reaction was charged to ˜600 psi of H2 at room temperature
  5. temperaturecooled to room temperature
  6. filtrationthe reaction mixture was filtered through a Celite® pad
  7. concentrationThe filtrate was concentrated
  8. custompurified by column chromatography on SiO2 (gradient, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-10c702cc5e53493f884f6179c29bdd8d
Source dataset
uspto-grants-2016_02
Patent number
US09265253B2

Reaction notes

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